Systemic oxidative stress associated with lung resection during single lung ventilation

We thank Dr Schachner for his interest and comments on our recent experimental findings [1]. The first facet of our study was that although initially (at 1 month), neointima formation in vein grafts was inhibited by perivenous application of fibrin glue at the time of implantation, at 4 months neointimal formation was not significantly different from controls [1]. Dr Schachner has implied that this is of no consequence. It is a widely held view that neointima formation is axiomatic in promoting vein graft failure [2]. The study therefore demonstrates that there may be a rebound effect that is manifest over the longer term. This also indicates that with acute or pulse treatments of vein grafts with fibrin glue or indeed cytostatic drugs or even gene transfer, care should be exercised when assessing effects at one month only and that potential rebound effects at later time points should be taken into account. Secondly, Dr Schachner has also suggested that increased medial thickening but no change in luminal area in response to fibrin glue at 4 months could be perceived as a ‘‘positive remodeling’’ effect. We accept that medial thickening is a necessary adaptive response of saphenous vein grafts to arterial conditions and have stated so on many occasions [3,4]. However, excessive thickening of the media may be equally as deleterious as neointima formation. Since medial thickening involves the proliferation of vascular smooth muscle cells and the deposition of matrix proteins, our data at 4 months indicate that these key events are actively occurring in these vein grafts at this time point. Although we did not study effect of fibrin glue in the longer term, it is reasonable to suggest that the trend toward excessive thickening may continue. Indeed, graft thickening in man has long been recognized to become clinically significant at 12—24 months after surgery [2], that is, over more prolonged time courses. Furthermore, vein graft hyperplasia is more aggressive at the anastomoses of vein into artery grafts, sites at which fibrin glue may be applied by surgeons to prevent bleeding. Fibrin glue may be particularly deleterious at these sites by augmenting hyperplasia. Such effects are perhaps not surprising since fibrin is a potent mitogen for vascular smooth muscle cells [5]. Thus, despite the interesting views of Dr Schachner, we reaffirm our conclusions that the application of fibrin glue may elicit untoward effects on vein graft thickening that in the long term may compromise vein graft patency.